الفهرس | Only 14 pages are availabe for public view |
Abstract CML is a myeloproliferative neoplasm that results from an acquired genetic change in a pluripotent haemopoietic stem cell. This altered stem cell proliferates and generates a population of differentiated cells that gradually displaces normal haemopoiesis and leads to a greatly expanded total myeloid mass (especially, predominant proliferation of granulocytic cells). It is associated with a characteristic chromosomal translocation called the Philadelphia chromosome (Victor et al., 2011). BCR-ABL protein is the pathophysiologic cause of chronic myeloid leukemia due to its action as a tyrosine kinase, targeted therapies (the first of which was imatinib mesylate) that specifically inhibit the activity of the BCR-ABL protein have been developed. These tyrosine kinase inhibitors can induce complete remissions in CML, confirming the central importance of BCR ABL as the cause of CML (Hehlmann et al., 2007). P53 is a tumor suppressor protein which has many mechanisms of anticancer function, and plays a role in apoptosis, genomic stability, and inhibition of angiogenesis.(Gilbert and Scott, 2008). P53 polymorphism inhibits the in vitro and in vivo response to imatinib without preventing BCR-ABL kinase inhibition. P53 is selectively activated by imatinib in BCR-ABL-expressing cells as a result of BCR-ABL kinase inhibition. Concordantly, p53 mutations are associated with progression to imatinib resistance in some human CMLs (Wendel et al., 2006). |